SARS-CoV-2 self-test uptake and factors associated with self-testing during Omicron BA.1 and BA.2 waves in France, January to May 2022.

BackgroundFollowing the SARS-CoV-2 Omicron variant spread, the use of unsupervised antigenic rapid diagnostic tests (self-tests) increased.AimThis study aimed to measure self-test uptake and factors associated with self-testing.MethodsIn this cross-sectional study from 20 January to 2 May 2022, the case series from a case-control study on factors associated with SARS-CoV-2 infection were used to analyse self-testing habits in France. A multivariable quasi-Poisson regression was used to explore the variables associated with self-testing among symptomatic cases who were not contacts of another infected individual. The control series from the same study was used as a proxy for the self-test background rate in the non-infected population of France.ResultsDuring the study period, 179,165 cases who tested positive through supervised tests were recruited. Of these, 64.7% had performed a self-test in the 3 days preceding this supervised test, of which 79,038 (68.2%) were positive. The most frequently reported reason for self-testing was the presence of symptoms (64.6%). Among symptomatic cases who were not aware of being contacts of another case, self-testing was positively associated with being female, higher education, household size, being a teacher and negatively associated with older age, not French by birth, healthcare-related work and immunosuppression. Among the control series, 12% self-tested during the 8 days preceding questionnaire filling, with temporal heterogeneity.ConclusionThe analysis showed high self-test uptake in France with some inequalities which must be addressed through education and facilitated access (cost and availability) for making it a more efficient epidemic control tool.

SARS-CoV-2 incubation period across variants of concern, individual factors, and circumstances of infection in France: a case series analysis from the ComCor study.

BACKGROUND: The incubation period of SARS-CoV-2 has been estimated for the known variants of concern. However, differences in study designs and settings make comparing variants difficult. We aimed to estimate the incubation period for each variant of concern compared with the historical strain within a unique and large study to identify individual factors and circumstances associated with its duration. METHODS: In this case series analysis, we included participants (aged ≥18 years) of the ComCor case-control study in France who had a SARS-CoV-2 diagnosis between Oct 27, 2020, and Feb 4, 2022. Eligible participants were those who had the historical strain or a variant of concern during a single encounter with a known index case who was symptomatic and for whom the incubation period could be established, those who reported doing a reverse-transcription-PCR (RT-PCR) test, and those who were symptomatic by study completion. Sociodemographic and clinical characteristics, exposure information, circumstances of infection, and COVID-19 vaccination details were obtained via an online questionnaire, and variants were established through variant typing after RT-PCR testing or by matching the time that a positive test was reported with the predominance of a specific variant. We used multivariable linear regression to identify factors associated with the duration of the incubation period (defined as the number of days from contact with the index case to symptom onset). FINDINGS: 20 413 participants were eligible for inclusion in this study. Mean incubation period varied across variants: 4·96 days (95% CI 4·90-5·02) for alpha (B.1.1.7), 5·18 days (4·93-5·43) for beta (B.1.351) and gamma (P.1), 4·43 days (4·36-4·49) for delta (B.1.617.2), and 3·61 days (3·55-3·68) for omicron (B.1.1.529) compared with 4·61 days (4·56-4·66) for the historical strain. Participants with omicron had a shorter incubation period than participants with the historical strain (-0·9 days, 95% CI -1·0 to -0·7). The incubation period increased with age (participants aged ≥70 years had an incubation period 0·4 days [0·2 to 0·6] longer than participants aged 18-29 years), in female participants (by 0·1 days, 0·0 to 0·2), and in those who wore a mask during contact with the index case (by 0·2 days, 0·1 to 0·4), and was reduced in those for whom the index case was symptomatic (-0·1 days, -0·2 to -0·1). These data were robust to sensitivity analyses correcting for an over-reporting of incubation periods of 7 days. INTERPRETATION: SARS-CoV-2 incubation period is notably reduced in omicron cases compared with all other variants of concern, in young people, after transmission from a symptomatic index case, after transmission to a maskless secondary case, and (to a lesser extent) in men. These findings can inform future COVID-19 contact-tracing strategies and modelling. FUNDING: Institut Pasteur, the French National Agency for AIDS Research-Emerging Infectious Diseases, Fondation de France, the INCEPTION project, and the Integrative Biology of Emerging Infectious Diseases project.

Early chains of transmission of COVID-19 in France, January to March 2020.

IntroductionSARS-CoV-2, the virus that causes COVID-19, has spread rapidly worldwide. In January 2020, a surveillance system was implemented in France for early detection of cases and their contacts to help limit secondary transmissions.AimTo use contact-tracing data collected during the initial phase of the COVID-19 pandemic to better characterise SARS-CoV-2 transmission.MethodsWe analysed data collected during contact tracing and retrospective epidemiological investigations in France from 24 January to 30 March 2020. We assessed the secondary clinical attack rate and characterised the risk of a contact becoming a case. We described chains of transmission and estimated key parameters of spread.ResultsDuring the study period, 6,082 contacts of 735 confirmed cases were traced. The overall secondary clinical attack rate was 4.1% (95% confidence interval (CI): 3.6-4.6), increasing with age of index case and contact. Compared with co-workers/friends, family contacts were at higher risk of becoming cases (adjusted odds ratio (AOR): 2.1, 95% CI: 1.4-3.0) and nosocomial contacts were at lower risk (AOR: 0.3, 95% CI: 0.1-0.7). Of 328 infector/infectee pairs, 49% were family members. The distribution of secondary cases was highly over-dispersed: 80% of secondary cases were caused by 10% of cases. The mean serial interval was 5.1 days (interquartile range (IQR): 2-8 days) in contact tracing pairs, where late transmission events may be censored, and 6.8 (3-8) days in pairs investigated retrospectively.ConclusionThis study increases knowledge of SARS-CoV-2 transmission, including the importance of superspreading events during the onset of the pandemic.

Impact of the Omicron variant on SARS-CoV-2 reinfections in France, March 2021 to February 2022.

Since the first reports in summer 2020, SARS-CoV-2 reinfections have raised concerns about the immunogenicity of the virus, which will affect SARS-CoV-2 epidemiology and possibly the burden of COVID-19 on our societies in the future. This study provides data on the frequency and characteristics of possible reinfections, using the French national COVID-19 testing database. The Omicron variant had a large impact on the frequency of possible reinfections in France, which represented 3.8% of all confirmed COVID-19 cases since December 2021.

Impact of SARS-CoV-2 Delta variant on incubation, transmission settings and vaccine effectiveness: Results from a nationwide case-control study in France.

BACKGROUND: We aimed to assess the settings and activities associated with SARS-CoV-2 infection in the context of B.1.617.2 (Delta) variant circulation in France, as well as the protection against symptomatic Delta infection. METHODS: In this nationwide case-control study, cases were SARS-CoV-2 infected adults recruited between 23 May and 13 August 2021. Controls were non-infected adults from a national representative panel matched to cases by age, sex, region, population density and calendar week. Participants completed an online questionnaire and multivariable logistic regression analysis was used to determine the association between acute SARS-CoV-2 infection and recent activity-related exposures, past history of SARS-CoV-2 infection, and COVID-19 vaccination. FINDINGS: We did not find any differences in the settings and activities associated with Delta versus non-Delta infections and grouped them for subsequent analyses. In multivariable analysis involving 12634 cases (8644 Delta and 3990 non-Delta) and 5560 controls, we found individuals under 40 years and attending bars (aOR:1.9; 95%CI:1.6-2.2) or parties (aOR:3.4; 95%CI:2.8-4.2) to be at increased risk of infection. In those aged 40 years and older, having children attend daycare (aOR:1.9; 95%CI:1.1-3.3), kindergarten (aOR:1.6; 95%CI:1.2-2.1), primary school (aOR:1.4; 95%CI:1.2-1.6) or middle school (aOR:1.3; 95%CI:1.2-1.6) were associated with increased risk of infection. We found strong protection against symptomatic Delta infection for those with prior infection whether it was recent (2-6 months) (95%; 95%CI:90-97) or associated with one dose (85%; 95%CI:78-90) or two doses of mRNA vaccine (96%; 95%CI:87-99). For those without past infection, protection was lower with two doses of mRNA vaccine (67%; 95%CI:63-71). INTERPRETATION: In line with other observational studies, we find reduced vaccine effectiveness against symptomatic Delta infections. The settings and activities at increased risk of infection indicate where efforts to reinforce individual and public health measures need to be concentrated.

Impact of original, B.1.1.7, and B.1.351/P.1 SARS-CoV-2 lineages on vaccine effectiveness of two doses of COVID-19 mRNA vaccines: Results from a nationwide case-control study in France.

BACKGROUND: We aimed to assess the effectiveness of two doses of mRNA COVID-19 vaccines against COVID-19 with the original virus and other lineages circulating in France. METHODS: In this nationwide case-control study, cases were SARS-CoV-2 infected adults with onset of symptoms between 14 February and 3 May 2021. Controls were non-infected adults from a national representative panel matched to cases by age, sex, region, population density and calendar week. Participants completed an online questionnaire on recent activity-related exposures and vaccination history. Information about the infecting virus was based on a screening RT-PCR for either B.1.1.7 or B.1.351/P.1 variants. FINDINGS: Included in our analysis were 7 288 adults infected with the original SARS-CoV-2 virus, 31 313 with the B.1.1.7 lineage, 2 550 with B.1.351/P1 lineages, and 3 644 controls. In multivariable analysis, the vaccine effectiveness (95% confidence interval) seven days after the second dose of mRNA vaccine was estimated at 88% (81-92), 86% (81-90) and 77% (63-86) against COVID-19 with the original virus, the B.1.1.7 lineage, and the B.1.351/P.1 lineages, respectively. Recent (2 to 6 months) history of virologically confirmed SARS-CoV-2 infection was found to be 83% (76-88), 88% (85-91) and 83% (71-90) protective against COVID-19 with the original virus, the B.1.1.7 lineage, and the B.1.351/P.1 lineages, respectively; and more distant (> 6 months) infections were 76% (54-87), 84% (75-90), and 74% (41-89) protective against COVID-19 with the original virus, the B.1.1.7 lineage, and the B.1.351/P.1 lineages, respectively. INTERPRETATION: In real-life settings, two doses of mRNA vaccines proved to be effective against COVID-19 with the original virus, B.1.1.7 lineage and B.1.351/P.1 lineages. FUNDING: Institut Pasteur, Research & Action Emerging Infectious Diseases (REACTing), Fondation de France (Alliance "Tous unis contre le virus").

Exposures associated with SARS-CoV-2 infection in France: A nationwide online case-control study.

BACKGROUND: We aimed to assess the role of different setting and activities in acquiring SARS-CoV-2 infection. METHODS: In this nationwide case-control study, cases were SARS-CoV-2 infected adults recruited between 27 October and 30 November 2020. Controls were individuals from the Ipsos market research database matched to cases by age, sex, region, population density and time period. Participants completed an online questionnaire on recent activity-related exposures. FINDINGS: Among 3426 cases and 1713 controls, in multivariable analysis, we found an increased risk of infection associated with any additional person living in the household (adjusted-OR: 1•16; 95%CI: 1•11-1•21); having children attending day-care (aOR: 1•31; 95%CI: 1•02-1•62), kindergarten (aOR: 1•27; 95%CI: 1•09-1•45), middle school (aOR: 1•30; 95%CI: 1•15-1•47), or high school (aOR: 1•18; 95%CI: 1•05-1•34); with attending professional (aOR: 1•15; 95%CI: 1•04-1•26) or private gatherings (aOR: 1•57; 95%CI: 1•45-1•71); and with having frequented bars and restaurants (aOR: 1•95; 95%CI: 1•76-2•15), or having practiced indoor sports activities (aOR: 1•36; 95%CI: 1•15-1•62). We found no increase in risk associated with frequenting shops, cultural or religious gatherings, or with transportation, except for carpooling (aOR: 1•47; 95%CI: 1•28-1•69). Teleworking was associated with decreased risk of infection (aOR: 0•65; 95%CI: 0•56-0•75). INTERPRETATION: Places and activities during which infection prevention and control measures may be difficult to fully enforce were those with increased risk of infection. Children attending day-care, kindergarten, middle and high schools, but not primary schools, were potential sources of infection for the household. FUNDING: Institut Pasteur, Research & Action Emerging Infectious Diseases (REACTing), Fondation de France (Alliance" Tous unis contre le virus").

Cluster of Coronavirus Disease 2019 (COVID-19) in the French Alps, February 2020.

BACKGROUND: On 7 February 2020, French Health authorities were informed of a confirmed case of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in an Englishman infected in Singapore who had recently stayed in a chalet in the French Alps. We conducted an investigation to identify secondary cases and interrupt transmission. METHODS: We defined as a confirmed case a person linked to the chalet with a positive reverse-transcription polymerase chain reaction sample for SARS-CoV-2. RESULTS: The index case stayed 4 days in the chalet with 10 English tourists and a family of 5 French residents; SARS-CoV-2 was detected in 5 individuals in France, 6 in England (including the index case), and 1 in Spain (overall attack rate in the chalet: 75%). One pediatric case, with picornavirus and influenza A coinfection, visited 3 different schools while symptomatic. One case was asymptomatic, with similar viral load as that of a symptomatic case. Seven days after the first cases were diagnosed, 1 tertiary case was detected in a symptomatic patient with from the chalet a positive endotracheal aspirate; all previous and concurrent nasopharyngeal specimens were negative. Additionally, 172 contacts were monitored; all contacts tested for SARS-CoV-2 (N = 73) were negative. CONCLUSIONS: The occurrence in this cluster of 1 asymptomatic case with similar viral load as a symptomatic patient suggests transmission potential of asymptomatic individuals. The fact that an infected child did not transmit the disease despite close interactions within schools suggests potential different transmission dynamics in children. Finally, the dissociation between upper and lower respiratory tract results underscores the need for close monitoring of the clinical evolution of suspected cases of coronavirus disease 2019.

Clinical and virological data of the first cases of COVID-19 in Europe: a case series.

BACKGROUND: On Dec 31, 2019, China reported a cluster of cases of pneumonia in people at Wuhan, Hubei Province. The responsible pathogen is a novel coronavirus, named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We report the relevant features of the first cases in Europe of confirmed infection, named coronavirus disease 2019 (COVID-19), with the first patient diagnosed with the disease on Jan 24, 2020. METHODS: In this case series, we followed five patients admitted to Bichat-Claude Bernard University Hospital (Paris, France) and Pellegrin University Hospital (Bordeaux, France) and diagnosed with COVID-19 by semi-quantitative RT-PCR on nasopharyngeal swabs. We assessed patterns of clinical disease and viral load from different samples (nasopharyngeal and blood, urine, and stool samples), which were obtained once daily for 3 days from hospital admission, and once every 2 or 3 days until patient discharge. All samples were refrigerated and shipped to laboratories in the National Reference Center for Respiratory Viruses (The Institut Pasteur, Paris, and Hospices Civils de Lyon, Lyon, France), where RNA extraction, real-time RT-PCR, and virus isolation and titration procedures were done. FINDINGS: The patients were three men (aged 31 years, 48 years, and 80 years) and two women (aged 30 years and 46 years), all of Chinese origin, who had travelled to France from China around mid-January, 2020. Three different clinical evolutions are described: (1) two paucisymptomatic women diagnosed within a day of exhibiting symptoms, with high nasopharyngeal titres of SARS-CoV-2 within the first 24 h of the illness onset (5·2 and 7·4 log10 copies per 1000 cells, respectively) and viral RNA detection in stools; (2) a two-step disease progression in two young men, with a secondary worsening around 10 days after disease onset despite a decreasing viral load in nasopharyngeal samples; and (3) an 80-year-old man with a rapid evolution towards multiple organ failure and a persistent high viral load in lower and upper respiratory tract with systemic virus dissemination and virus detection in plasma. The 80-year-old patient died on day 14 of illness (Feb 14, 2020); all other patients had recovered and been discharged by Feb 19, 2020. INTERPRETATION: We illustrated three different clinical and biological types of evolution in five patients infected with SARS-CoV-2 with detailed and comprehensive viral sampling strategy. We believe that these findings will contribute to a better understanding of the natural history of the disease and will contribute to advances in the implementation of more efficient infection control strategies. FUNDING: REACTing (Research & Action Emerging Infectious Diseases).

First cases of coronavirus disease 2019 (COVID-19) in France: surveillance, investigations and control measures, January 2020.

A novel coronavirus (severe acute respiratory syndrome coronavirus 2, SARS-CoV-2) causing a cluster of respiratory infections (coronavirus disease 2019, COVID-19) in Wuhan, China, was identified on 7 January 2020. The epidemic quickly disseminated from Wuhan and as at 12 February 2020, 45,179 cases have been confirmed in 25 countries, including 1,116 deaths. Strengthened surveillance was implemented in France on 10 January 2020 in order to identify imported cases early and prevent secondary transmission. Three categories of risk exposure and follow-up procedure were defined for contacts. Three cases of COVID-19 were confirmed on 24 January, the first cases in Europe. Contact tracing was immediately initiated. Five contacts were evaluated as at low risk of exposure and 18 at moderate/high risk. As at 12 February 2020, two cases have been discharged and the third one remains symptomatic with a persistent cough, and no secondary transmission has been identified. Effective collaboration between all parties involved in the surveillance and response to emerging threats is required to detect imported cases early and to implement adequate control measures.